CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria

1. Children older than 2 years or adults, male and female in both groups.
2. Patients CD1a antigen blast expression ≥20% at inclusion, either immunophenotypically (flow cytometry) or histologically confirmed.
3. R/R CD1a-positive T-ALL/LL patients defined as:

   * Failure to achieve morphological complete remission (\> 5% bone marrow blasts) or persistence of extramedullary disease after at least two cycles of chemotherapy.
   * First or subsequent relapse, including morphologic or MRD-detectable (≥1x10-4 ) bone marrow and/or extramedullary relapses after at least one standard frontline therapy.
   * Relapse after allogeneic haematopoietic stem cell transplantation (allo-HSCT).
   * Primary refractoriness, defined as either morphologic persistence or detectable MRD (≥1x10-4 ) after at least two cycles of chemotherapy, making the patient not candidate for allo-HSCT.
4. Patient without reproductive capacity or else, commitment to the use of a highly effective method of contraception during the study.

Exclusion Criteria:

1. Limiting organ dysfunction, such as uncontrolled cardiac (e.g., depressed left ventricular ejection fraction (LVEF), \<45%), pulmonary, liver, renal or CNS dysfunction.
2. Allo-HSCT within a time frame \<3 months, or requiring continued immunosuppressive treatment for graft versus host disease (GvHD).
3. Uncontrolled epilepsy or underlying central nervous system (CNS) severe disease.
4. Active bacterial, fungal or viral infection not controlled by adequate treatment.
5. Known HIV, active hepatitis B (HBV), or hepatitis C virus (HCV) infection.
6. Women who are pregnant (urine/blood pregnancy test positive) or lactating.
7. Severe illness or medical condition, which would not permit the patient to be managed according to the protocol.
8. Suffering from a serious autoimmune disease or immunodeficiency disease.
9. The patient participated in other experimental drug clinical trial within 6 weeks prior to OC-1 infusion.
10. Other non-controlled concomitant neoplasms.

主要终点：Number of adverse events grade III-IV · Number of adverse events grade III-IV using common toxicity criteria (CTC) · 1 year particularly the first 28 days after infusion；Incidence of severe Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) · Incidence of severe Cytokine release syndrome (CRS) (≥ grade III) and Immune effector cell-associated neurotoxicity syndrome (ICANS) (≥ grade II) · 1 year particularly the first 28 days after infusion；Non-relapse treatment-related mortality (NRM) · Non-relapse treatment-related mortality (NRM) · 1 year；Number of adverse events of special interest (AESI) · Number of adverse events of special interest (AESI) · 1 year；Assessment of the immunological homeostasis · Assessment of the immunological homeostasis, through the identification of lymphocytes subpopulations by flow cytometry at each study timepoint. · 1 year；Incidence of the treatment-related dermatological events · Incidence of the treatment-related dermatological events · 1 year
次要终点：Remission rate；Response rates；Complete remission duration (CRD)；Duration of remission；Minimal residual disease (MRD) response；Progression-free survival (PFS)；Overall survival；Persistence of OC-1

• Experimental: CD1a-CAR T · EXPERIMENTAL · CD1a CAR T cells transduced with a lentiviral vector to express CD1a chimeric receptor domain on T cells administered with a dose-escalation approach.

First in humans, exploratory, open-label, single-arm, multicentre, non-competitive, dose escalation study to assess the safety and efficacy of CD1a-CAR T therapy in patients with relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LL)